title: Synthesis, in vitro screening and in vivo evaluation of cyclic RGD analogs cyclized through oxorhenium and oxotechnetium coordination.
abstract: A library of RGD tripeptide analogs cyclized through oxorhenium coordination by an NS2/S chelation motif was synthesized. Screening towards integrins αVβ3, αIIbβ3 and αVβ5 led to the identification of 6 oxorhenium complexes that bind to integrin αVβ3 in the submicromolar range. In vivo evaluation of five of the corresponding oxotechnetium complexes using nude mice bearing a U87MG human tumor xenograft showed a significant and specific accumulation of radioactivity inside the tumor. The best results in vivo were obtained with complexes Tc-16 and Tc-50 that displayed a higher tumor accumulation and a lower distribution in other tissues relative to a reference cyclopentapeptide tracer.
authors.affiliation: CEA/Saclay, iBiTec-S/SIMOPRO, Bâtiment 152, 91191 Gif-sur-Yvette, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Aufort
authors.forename: Marta
authors.initials: M
authors.lastname: Gonera
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Lelait
authors.forename: Bertrand
authors.initials: B
authors.lastname: Czarny
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Clainche
authors.forename: Robert
authors.initials: R
authors.lastname: Thaï
authors.forename: Amandine
authors.initials: A
authors.lastname: Landra
authors.forename: Mathias
authors.initials: M
authors.lastname: Ruinart de Brimont
authors.forename: Christophe
authors.initials: C
authors.lastname: Dugave
mesh_terms: D000818:Animals; D003500:Cyclization; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D012211:Rhenium / Q000737:chemistry*; D013237:Stereoisomerism; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D009942:Organometallic Compounds; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; C015428:perrhenate; D012211:Rhenium; D013667:Technetium